Clinical, Biochemical and Radiological Features of an Infant Affected by Leigh Disease – A Case Report
Open Access Journal of Endocrinology
Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report
Aruna G1*, Vykuntaraju KG2, Ramesh RL3 and Basavaraja GV4
Case Report
1Department
of Biochemistry, Indira Gandhi Institute of Child Health, India
2Department
of Paediatric Neurology, Indira Gandhi Institute of Child Health, India
Received Date: February 08, 2017
3Department
of Radiology, Indira Gandhi Institute of Child Health, India
Published Date: February 27, 2017
4Department
of Pediatrics, Indira Gandhi Institute of Child Health, India
Volume 1 Issue 1
*Corresponding author: Aruna G, Department of Biochemistry, Indira Gandhi Institute of Child Health, Bengaluru,
Karnataka, India, E-mail: arug68@gmail.com
Abstract
Leigh disease, also known as subacute necrotising encephalomyelopathy (SNE), is a rare inherited progressive
neurometabolic life threatening mitochondrial disorder. Early diagnosis and early treatment will help in reducing both
morbidity and mortality associated with this disorder. We report a 2.5 months old Indian infant with clinical, biochemical
and radiological features of Leigh Disease. This is the first case report of a child with Leigh Disease of early onset.
Keywords: Leigh disease; Choreoathetosis; Globus pallidus; Genetic heterogeneity
Introduction
Leigh disease is a rare inherited progressive
neurometabolic, life threatening mitochondrial disorder.
It has extensive clinical, biochemical, neuroimaging and
genetic heterogeneity. Prevalence at birth is 1:40000[1].
It is transmitted as autosomal recessive, X- linked
recessive or as maternal inheritance. It is caused by
mutations in nuclear genes or mitochondrial genes[2].
Case Presentation
A two and a half month old male child, 1 st born to 2nd
degree consanguineously married couple as shown in
figure 1 with uneventful perinatal history, presented with
history of fever which subsided after 4 days, followed by
excessive cry, apnoeic spells and excessive arching of the
body since 2 days. There was no history of convulsions.
Development was appropriate for age. Family History:
There was no history of abortion or still birth. No history
of similar illness in the family.
Figure 1: Showing pedigree of the baby affected with
Leigh disease.
Clinical, Biochemical and Radiological Features of an Infant Affected by Leigh Disease - A Case Report
J Endocrinol
2
Open Access Journal of Endocrinology
2.
3.
4.
5.
Examination
The baby's weight was 4.5kg (3rd -50th percentile),
length was 58cm (3rd -50th percentile) and occipito frontal
circumference was 38cm (3rd -50th percentile). He was
pink, euthermic with no dysmorphic features. He had
excessive cry and was not consolable. He had long
inspiratory pause almost lasting for 30-40 seconds. His
pulse rate was 127/ min (120-160), respiratory rate was
44/min (20-40) and oxygen saturation was 77% (>92) @
Room Air. His capillary refill time was < 3 seconds (P). Platelet count
was 835000 cells per mm3 (150000-400000). Peripheral
smear showed normocytic normochromic blood picture
with reactive thrombocytosis. Prothrombin time was
16.8seconds (control 15), partial thromboplastin time
was 30.9 seconds (control 30). Random plasma glucose
was 85.1mg/dl ( 60-100), Urea was 26mg/dl (10-36),
Creatinine was 0.7mg/dl (0.2-0.4), ionized calcium was
5.1 mg/dl (4.8-4.92), serum C-reactive protein-12.8mg/L
(0.8-15.8), cerebrospinal fluid c-reactive protein was <
6mg/L(0.8-5.8), Cerebrospinal fluid analysis showed 3
cells, all lymphocytes with normal glucose and protein
levels. Arterial blood gas (ABG) analysis showed
metabolic acidosis with high anion gap as shown in table
1. Plasma ammonia was low. Arterial blood lactate and
CSF lactate were high as shown in Table 2.
Central Nervous System Examination
Baby was lethargic. Cranial nerves examination was
normal. There was hypertonia in both the lower limbs.
Power was 3/5 in all limbs. Deep tendon reflexes were
exaggerated with bilateral positive babinski sign. Pupils
were dilated and sluggishly reacting to light.
Choreoathetosis was noted. Newborn reflexes like sucking
and rooting reflexes were present. Fundus examination
was normal.
Other systems: Gaseous distension was present per
abdomen. His cardiovascular and respiratory systems
were normal.
Provisional Diagnosis
1.
Neurometabolic disorder
Table 1: Arterial blood gas analysis
Test
Result
Normal Value
Interpretation
pH
7.304
7.35-7.45
Acidosis
pCO2
20.3 mmHg
35-45
Low
pO2
100.7mm Hg
80-100
Normal
SO2
96.30%
80-100
Normal
HCO3-
9.9mEq/L
21-28
Low
BE
-15.1mEq/L
-7to +1
Low
Na+
134mEq/L
135-145
Low
K+
4.4mEq/L
3.5-6
Normal
Cl-
100mEq/L
98-106
Normal
Anion Gap
24.1mEq/L
7-16
High
Metabolic acidosis with high anion gap.
Table 2: Special biochemistry tests.
Test
Result
Plasma Ammonia 13 µg/dl
Lactate ( Arterial
32.9mg/dl
Blood)
Lactate ( CSF ) 26.9 mg/dl
Normal
Interpretation
Value
18-74
low
3.6-18
high
5.4-20
high
Aruna G et al. Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report. J Endocrinol 2017, 1(1): 000104.
Liver function test showed mild derangement with
aspartate transaminase 97 IU/L (15-55), alanine
transaminase 62 IU/L (5-45). Blood culture and CSF
culture showed no growth.ECG and Chest X Ray were
normal.
Copyright© Aruna G et al.
3
Open Access Journal of Endocrinology
CT Brain (Plain ) as shown in figure 2, at the level of
basal ganglia,
showed bilateral symmetrical
hypodensities noted in the putamen.
Figure 3: MRI Axial stir images at the level of basal ganglia
showing
diffuse
abnormal
hyperintensities
of
globuspallidus and putamen.
Figure 2: CT Brain (Plain) at the level of basal ganglia
showed bilateral symmetrical hypodensities noted in the
putamen.
MRI Brain showed
a.
b.
c.
d.
Symmetric abnormal signal intensities seen involving
bilateral globus pallidi and putamen appearing
hyperintense on T2W1, hypointense on T1W2 and
FLAIR sequences.
The involved areas showed diffusion restriction with
matched
Apparent
Diffusion
Co-efficient
hypointensity.
Diffuse frontotemporal atrophic changes are seen as
evidenced by widening of CSF spaces and prominent
basifrontal and basitemporal cisterns.
Degree of myelination appears adequate for patient’s
age
MRI Brain showed features suggestive of Leigh disease as
shown in Figures 3 and 4.
Figure 4: MRI Coronal diffusion weighted imaging at the
level of basal ganglia showing homogenous restricted
diffusion in bilateral basal ganglia.
Differential
diagnosis:
Hypoxic
ischemic
encephalopathy, metabolic encephalopathy.
Final Diagnosis: Leigh disease
Treatment: The baby was started on antibiotics,
anticonvulsants, thiamine, biotin, carnitine and
supportive therapy including mechanical ventilation for
impending respiratory failure. The baby improved over
the next four days and was later extubated. Post
extubation baby remained hemodynamically stable.
Outcome: The baby improved.
Discussion
The criteria for diagnosis of Leigh disease are
progressive neurological disease with motor and
Aruna G et al. Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report. J Endocrinol 2017, 1(1): 000104.
Copyright© Aruna G et al.
4
Open Access Journal of Endocrinology
intellectual developmental delay, signs and symptoms of
brainstem and / or basal ganglia disease, raised lactate in
blood and / or CSF, characteristic bilateral symmetric
necrotic lesions in the basal ganglia and / or brain stem.
Neuroimaging[3]: MRI plays a very important role in the
diagnosis
of
SNE.
The
most
characteristic
neuroradiological findings are bilateral symmetrical focal
hyperintensities in the basal ganglia, thalamus,
substantianigra and brainstem at various levels on T2W1
MRI. In the basal ganglia, the putamen is particularly
involved. Low attenuation in the putamen on CT is
considered to be characteristic of the disease. MR
Spectroscopy shows elevated lactate and choline and
depressed N-acetyl aspartate. Specific therapy for Leigh
syndrome is not available. The aim of supportive therapy
is to improve ATP production and reduce lactate levels.
Thiamine is reported to improve the neurological status
in some children. Marked improvement with riboflavin
was observed which nearly normalized the ATP
production. Use of intravenous soyabean oil resulted in
rapid clinical and biochemical improvement in children
with acute central respiratory failure. Ketogenic diet is
found to be useful in children with pyruvate
dehydrogenase complex deficiency. Coenzyme Q and
carnitine have also found to be effective. Intramuscular
botulinum toxin is found to provide relief from dystonia
in children having dystonia[4]. Pronuclear transfer ( PNT)
and maternal spindle transfer ( MST ) are two invitro
fertilization (IVF) based techniques which seem to have
the potential to prevent transmission of maternally
inherited Leigh disease caused by mutations in the
mitochondrial genes[5]. Egg donation, egg donation with
surrogacy or adoption can be an alternative for Leigh
disease caused by mutations in the nuclear genes.
Respiratory chain, pyruvate dehydrogenase complex and
pyruvate carboxylase enzymes assay, muscle biopsy and
mitochondrial gene mutation analysis could not be
performed due to paucity of facilities and financial
constraints.
Conclusion
Any child who presents to us with history of lethargy,
weakness, convulsions, abnormal breathing, abnormal
movements and encephalopathy should be investigated
further with ABG, electrolytes, arterial blood and CSF
lactate. If CT Brain shows evidence of brain stem or basal
ganglia hypodensity, it should be confirmed by MRI Brain
to establish the diagnosis of Leigh disease. The child must
be treated with mega doses of vitamins and care must be
taken to avoid stressful situations and infection.
Acknowledgements
We acknowledge Dr. Navin A Patil and Dr. Kunal Naidu,
Department of Radiology MG diagnostics, Bengaluru,
Karnataka, India for confirming the clinical diagnosis with
appropriate neuroimaging.
We acknowledge our Director, Dr. Asha Benakappa,
Indira Gandhi Institute of Child Health, Bengaluru,
Karnataka, India for constant encouragement and
support.
References
1.
Kartikasalwah AL, Ngu LH (2010) Leigh syndrome:
MRI findings in two children Biomed Imaging Interv J
6(1): e6.
2.
Richard E Behrman
6 Nelson’s Text Book Of
Paediatrics 20th Edition. Saunders Ltd, Pennsylvania
pp. 2902.
This baby presented to us at 2.5 months with excessive
cry, breathing difficulty, arching of the body and apneic
spells which pointed towards a neurometabolic disorder.
ABG showed metabolic acidosis with high anion gap.
Blood and CSF lactate were elevated. CT Brain (plain)
showed features suggestive of Leigh disease which was
confirmed by MRI Brain. This baby was treated with
antibiotics, thiamine, riboflavin, carnitine, biotin and
supportive therapy including mechanical ventilation for
impending respiratory failure which was considered to be
factors contributing to his improvement.
3.
Shrikhande, Piyush K, Aarif MMS, Kunal A, Gurmeet S
(2010) A rare mitochondrial disorder: Leigh
syndrome - a case report. Italian Journal of Pediatrics
36: 62.
4.
Presently, the baby is 2.5 years old. He is recovering
from the acute episode. He is able to walk with support.
His developmental quotient is 13 months. Nuclear gene
study has been done for this baby. Mutation was not
found. Mitochondrial gene study from muscle biopsy
specimen is planned. To our knowledge, this is the first
case detected at an early age of 2.5months with clinical,
biochemical and radiological features of Leigh disease.
Chae-Woo Chung, Suhng-Hee H, Young-Chul C, YoungHo S, Jin-Soo K, et al. 99 A Case of Leigh’s Disease
with Initial Manifestation of Dystonia. Yonsei Medical
Journal 31(2): 274-279.
5. Po-Cheng H, Huei-Shyong W (2007) A previously
undescribed leukodystrophy in Leigh syndrome
associated with T9176C mutation of the
mitochondrial ATPase 6 gene. Developmental
Medicine & Child Neurology 49(1): 65-67.
Aruna G et al. Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report. J Endocrinol 2017, 1(1): 000104.
Copyright© Aruna G et al.
Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report
Aruna G1*, Vykuntaraju KG2, Ramesh RL3 and Basavaraja GV4
Case Report
1Department
of Biochemistry, Indira Gandhi Institute of Child Health, India
2Department
of Paediatric Neurology, Indira Gandhi Institute of Child Health, India
Received Date: February 08, 2017
3Department
of Radiology, Indira Gandhi Institute of Child Health, India
Published Date: February 27, 2017
4Department
of Pediatrics, Indira Gandhi Institute of Child Health, India
Volume 1 Issue 1
*Corresponding author: Aruna G, Department of Biochemistry, Indira Gandhi Institute of Child Health, Bengaluru,
Karnataka, India, E-mail: arug68@gmail.com
Abstract
Leigh disease, also known as subacute necrotising encephalomyelopathy (SNE), is a rare inherited progressive
neurometabolic life threatening mitochondrial disorder. Early diagnosis and early treatment will help in reducing both
morbidity and mortality associated with this disorder. We report a 2.5 months old Indian infant with clinical, biochemical
and radiological features of Leigh Disease. This is the first case report of a child with Leigh Disease of early onset.
Keywords: Leigh disease; Choreoathetosis; Globus pallidus; Genetic heterogeneity
Introduction
Leigh disease is a rare inherited progressive
neurometabolic, life threatening mitochondrial disorder.
It has extensive clinical, biochemical, neuroimaging and
genetic heterogeneity. Prevalence at birth is 1:40000[1].
It is transmitted as autosomal recessive, X- linked
recessive or as maternal inheritance. It is caused by
mutations in nuclear genes or mitochondrial genes[2].
Case Presentation
A two and a half month old male child, 1 st born to 2nd
degree consanguineously married couple as shown in
figure 1 with uneventful perinatal history, presented with
history of fever which subsided after 4 days, followed by
excessive cry, apnoeic spells and excessive arching of the
body since 2 days. There was no history of convulsions.
Development was appropriate for age. Family History:
There was no history of abortion or still birth. No history
of similar illness in the family.
Figure 1: Showing pedigree of the baby affected with
Leigh disease.
Clinical, Biochemical and Radiological Features of an Infant Affected by Leigh Disease - A Case Report
J Endocrinol
2
Open Access Journal of Endocrinology
2.
3.
4.
5.
Examination
The baby's weight was 4.5kg (3rd -50th percentile),
length was 58cm (3rd -50th percentile) and occipito frontal
circumference was 38cm (3rd -50th percentile). He was
pink, euthermic with no dysmorphic features. He had
excessive cry and was not consolable. He had long
inspiratory pause almost lasting for 30-40 seconds. His
pulse rate was 127/ min (120-160), respiratory rate was
44/min (20-40) and oxygen saturation was 77% (>92) @
Room Air. His capillary refill time was < 3 seconds (P). Platelet count
was 835000 cells per mm3 (150000-400000). Peripheral
smear showed normocytic normochromic blood picture
with reactive thrombocytosis. Prothrombin time was
16.8seconds (control 15), partial thromboplastin time
was 30.9 seconds (control 30). Random plasma glucose
was 85.1mg/dl ( 60-100), Urea was 26mg/dl (10-36),
Creatinine was 0.7mg/dl (0.2-0.4), ionized calcium was
5.1 mg/dl (4.8-4.92), serum C-reactive protein-12.8mg/L
(0.8-15.8), cerebrospinal fluid c-reactive protein was <
6mg/L(0.8-5.8), Cerebrospinal fluid analysis showed 3
cells, all lymphocytes with normal glucose and protein
levels. Arterial blood gas (ABG) analysis showed
metabolic acidosis with high anion gap as shown in table
1. Plasma ammonia was low. Arterial blood lactate and
CSF lactate were high as shown in Table 2.
Central Nervous System Examination
Baby was lethargic. Cranial nerves examination was
normal. There was hypertonia in both the lower limbs.
Power was 3/5 in all limbs. Deep tendon reflexes were
exaggerated with bilateral positive babinski sign. Pupils
were dilated and sluggishly reacting to light.
Choreoathetosis was noted. Newborn reflexes like sucking
and rooting reflexes were present. Fundus examination
was normal.
Other systems: Gaseous distension was present per
abdomen. His cardiovascular and respiratory systems
were normal.
Provisional Diagnosis
1.
Neurometabolic disorder
Table 1: Arterial blood gas analysis
Test
Result
Normal Value
Interpretation
pH
7.304
7.35-7.45
Acidosis
pCO2
20.3 mmHg
35-45
Low
pO2
100.7mm Hg
80-100
Normal
SO2
96.30%
80-100
Normal
HCO3-
9.9mEq/L
21-28
Low
BE
-15.1mEq/L
-7to +1
Low
Na+
134mEq/L
135-145
Low
K+
4.4mEq/L
3.5-6
Normal
Cl-
100mEq/L
98-106
Normal
Anion Gap
24.1mEq/L
7-16
High
Metabolic acidosis with high anion gap.
Table 2: Special biochemistry tests.
Test
Result
Plasma Ammonia 13 µg/dl
Lactate ( Arterial
32.9mg/dl
Blood)
Lactate ( CSF ) 26.9 mg/dl
Normal
Interpretation
Value
18-74
low
3.6-18
high
5.4-20
high
Aruna G et al. Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report. J Endocrinol 2017, 1(1): 000104.
Liver function test showed mild derangement with
aspartate transaminase 97 IU/L (15-55), alanine
transaminase 62 IU/L (5-45). Blood culture and CSF
culture showed no growth.ECG and Chest X Ray were
normal.
Copyright© Aruna G et al.
3
Open Access Journal of Endocrinology
CT Brain (Plain ) as shown in figure 2, at the level of
basal ganglia,
showed bilateral symmetrical
hypodensities noted in the putamen.
Figure 3: MRI Axial stir images at the level of basal ganglia
showing
diffuse
abnormal
hyperintensities
of
globuspallidus and putamen.
Figure 2: CT Brain (Plain) at the level of basal ganglia
showed bilateral symmetrical hypodensities noted in the
putamen.
MRI Brain showed
a.
b.
c.
d.
Symmetric abnormal signal intensities seen involving
bilateral globus pallidi and putamen appearing
hyperintense on T2W1, hypointense on T1W2 and
FLAIR sequences.
The involved areas showed diffusion restriction with
matched
Apparent
Diffusion
Co-efficient
hypointensity.
Diffuse frontotemporal atrophic changes are seen as
evidenced by widening of CSF spaces and prominent
basifrontal and basitemporal cisterns.
Degree of myelination appears adequate for patient’s
age
MRI Brain showed features suggestive of Leigh disease as
shown in Figures 3 and 4.
Figure 4: MRI Coronal diffusion weighted imaging at the
level of basal ganglia showing homogenous restricted
diffusion in bilateral basal ganglia.
Differential
diagnosis:
Hypoxic
ischemic
encephalopathy, metabolic encephalopathy.
Final Diagnosis: Leigh disease
Treatment: The baby was started on antibiotics,
anticonvulsants, thiamine, biotin, carnitine and
supportive therapy including mechanical ventilation for
impending respiratory failure. The baby improved over
the next four days and was later extubated. Post
extubation baby remained hemodynamically stable.
Outcome: The baby improved.
Discussion
The criteria for diagnosis of Leigh disease are
progressive neurological disease with motor and
Aruna G et al. Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report. J Endocrinol 2017, 1(1): 000104.
Copyright© Aruna G et al.
4
Open Access Journal of Endocrinology
intellectual developmental delay, signs and symptoms of
brainstem and / or basal ganglia disease, raised lactate in
blood and / or CSF, characteristic bilateral symmetric
necrotic lesions in the basal ganglia and / or brain stem.
Neuroimaging[3]: MRI plays a very important role in the
diagnosis
of
SNE.
The
most
characteristic
neuroradiological findings are bilateral symmetrical focal
hyperintensities in the basal ganglia, thalamus,
substantianigra and brainstem at various levels on T2W1
MRI. In the basal ganglia, the putamen is particularly
involved. Low attenuation in the putamen on CT is
considered to be characteristic of the disease. MR
Spectroscopy shows elevated lactate and choline and
depressed N-acetyl aspartate. Specific therapy for Leigh
syndrome is not available. The aim of supportive therapy
is to improve ATP production and reduce lactate levels.
Thiamine is reported to improve the neurological status
in some children. Marked improvement with riboflavin
was observed which nearly normalized the ATP
production. Use of intravenous soyabean oil resulted in
rapid clinical and biochemical improvement in children
with acute central respiratory failure. Ketogenic diet is
found to be useful in children with pyruvate
dehydrogenase complex deficiency. Coenzyme Q and
carnitine have also found to be effective. Intramuscular
botulinum toxin is found to provide relief from dystonia
in children having dystonia[4]. Pronuclear transfer ( PNT)
and maternal spindle transfer ( MST ) are two invitro
fertilization (IVF) based techniques which seem to have
the potential to prevent transmission of maternally
inherited Leigh disease caused by mutations in the
mitochondrial genes[5]. Egg donation, egg donation with
surrogacy or adoption can be an alternative for Leigh
disease caused by mutations in the nuclear genes.
Respiratory chain, pyruvate dehydrogenase complex and
pyruvate carboxylase enzymes assay, muscle biopsy and
mitochondrial gene mutation analysis could not be
performed due to paucity of facilities and financial
constraints.
Conclusion
Any child who presents to us with history of lethargy,
weakness, convulsions, abnormal breathing, abnormal
movements and encephalopathy should be investigated
further with ABG, electrolytes, arterial blood and CSF
lactate. If CT Brain shows evidence of brain stem or basal
ganglia hypodensity, it should be confirmed by MRI Brain
to establish the diagnosis of Leigh disease. The child must
be treated with mega doses of vitamins and care must be
taken to avoid stressful situations and infection.
Acknowledgements
We acknowledge Dr. Navin A Patil and Dr. Kunal Naidu,
Department of Radiology MG diagnostics, Bengaluru,
Karnataka, India for confirming the clinical diagnosis with
appropriate neuroimaging.
We acknowledge our Director, Dr. Asha Benakappa,
Indira Gandhi Institute of Child Health, Bengaluru,
Karnataka, India for constant encouragement and
support.
References
1.
Kartikasalwah AL, Ngu LH (2010) Leigh syndrome:
MRI findings in two children Biomed Imaging Interv J
6(1): e6.
2.
Richard E Behrman
6 Nelson’s Text Book Of
Paediatrics 20th Edition. Saunders Ltd, Pennsylvania
pp. 2902.
This baby presented to us at 2.5 months with excessive
cry, breathing difficulty, arching of the body and apneic
spells which pointed towards a neurometabolic disorder.
ABG showed metabolic acidosis with high anion gap.
Blood and CSF lactate were elevated. CT Brain (plain)
showed features suggestive of Leigh disease which was
confirmed by MRI Brain. This baby was treated with
antibiotics, thiamine, riboflavin, carnitine, biotin and
supportive therapy including mechanical ventilation for
impending respiratory failure which was considered to be
factors contributing to his improvement.
3.
Shrikhande, Piyush K, Aarif MMS, Kunal A, Gurmeet S
(2010) A rare mitochondrial disorder: Leigh
syndrome - a case report. Italian Journal of Pediatrics
36: 62.
4.
Presently, the baby is 2.5 years old. He is recovering
from the acute episode. He is able to walk with support.
His developmental quotient is 13 months. Nuclear gene
study has been done for this baby. Mutation was not
found. Mitochondrial gene study from muscle biopsy
specimen is planned. To our knowledge, this is the first
case detected at an early age of 2.5months with clinical,
biochemical and radiological features of Leigh disease.
Chae-Woo Chung, Suhng-Hee H, Young-Chul C, YoungHo S, Jin-Soo K, et al. 99 A Case of Leigh’s Disease
with Initial Manifestation of Dystonia. Yonsei Medical
Journal 31(2): 274-279.
5. Po-Cheng H, Huei-Shyong W (2007) A previously
undescribed leukodystrophy in Leigh syndrome
associated with T9176C mutation of the
mitochondrial ATPase 6 gene. Developmental
Medicine & Child Neurology 49(1): 65-67.
Aruna G et al. Clinical, Biochemical and Radiological Features of an Infant
Affected by Leigh Disease - A Case Report. J Endocrinol 2017, 1(1): 000104.
Copyright© Aruna G et al.